The research program outlined in this proposal is designed to investigate the physiology and biochemistry of macrophage effector functions, and the role(s) of membrane receptors for immune ligands such as IgG and complement in these processes. Macrophages are grown on substrates coated with immune ligands and the capacity of these ligands to modulate cell surface receptors is measured. Using this method we are able to isolate and analyze the substrate adherent segment of macrophage surface membrane. In another series of experiments we are examining the hypothesis that 2-deoxy-glucose and 2-deoxy-fluoromannose specifically inhibit Fc and complement receptor mediated phagocytosis by inhibiting the glycosylation, transport, and insertion of membrane glycoproteins into the cells surface. Also under study are ATP and creatine phosphate utilization and turnover during endocytosis, the mechanisms by which macrophages remove immune complexes from the surfaces of cells, and the role(s) of membrane receptors for immune ligands in pinocytosis. In a parallel series of experiments we are examining the anti-bacterial and anti-tumor effector systems of "activated" macrophages. For this purpose we are developing an extracellular bacteriocidal system using BCG elicited macrophages. Studies of tumorigenesis by B16 melanoma cells in C57BL/6J mice show that BCG elicited peritoneal exudate cells have the potential to inhibit tumorigenesis, but that tumor cell secretory products such as plasminogen activator may inhibit movement of leucocytes into the nascent tumor bed. Additional studies of the role(s) of macrophage secretory products in initiating and perpetuating inflammation and bacterial infection are planned.